The inferior colliculus (IC) is a major site of integration of virtually all ascending and descending projections of the central auditory system. Several fundamental physiological response properties of IC neurons are profoundly influenced by their inhibitory inputs. Some of the inhibition to IC originates locally, but significant inhibitory inputs to the IC arises from the superior olivary complex and the dorsal (DNLL) and ventral (VNLL) lemniscal nuclei. The long-term goal of this research program is to reveal cellular mechanisms of central auditory inhibitory circuits. The objective of this application is to clarify the functional role in hearing of the superior paraolivary nucleus (SPON), a prominent inhibitory nucleus of the superior olive that innervates the IC. Our central hypothesis is that the nature, distribution and timing of SPON inputs modulates responses of neurons in the VNLL, the DNLL and the IC. The first specific aim is to reveal the topography of intrinsic and sub-collicular projections of SPON by intracellular labeling of SPON cells in brain slices. The second specific aim is to uncover the convergence of inhibitory IC inputs originating from SPON, DNLL and VNLL. To do so, injections of distinct anterograde tracer molecules into the corresponding frequency regions of these nuclei will be examined by light and electron microscopy. The third aim is to determine the neurotransmitter basis of auditory evoked responses in SPON. Single-unit extracellular recording techniques will be used to study responses of SPON units to sounds before, during and after the iontophoretic application of receptor antagonists for the neurotransmitters GABA and glycine. Collectively, the results will provide insight into mechanisms of integration of inhibitory synapses that may be generalizable to other CNS circuits. Such information is necessary for advancements in technologies to repair genetically abnormal, damaged or degenerating parts of the brain .